The main reason why therapeutic schemes fail in Glioblastoma lies on its own peculiarities as a cancer and on our failure to fully decipher them. Fast tumor evolution, invasiveness and incomplete surgical resection contribute to disease recurrence, therapy resistance and high mortality. More faithful models must be developed to address Glioblastoma biology and better clinical guidance. Research studies are discussed in this review that: i) improve understanding and assessment of the growth mechanisms of Glioblastoma and ii) develop preclinical models (in vitro-in vivo-in silico) that mimic patient's tumor (phenocopying) in order to provide better prediction of response to therapies.
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http://dx.doi.org/10.1109/RBME.2021.3111744 | DOI Listing |
Attempts to activate an anti-tumor immune response in glioblastoma (GBM) have been met with many challenges due to its inherently immunosuppressive tumor microenvironment. The degree and mechanisms by which molecularly and phenotypically diverse tumor-propagating glioma stem cells (GSCs) contribute to this state are poorly defined. In this study, our multifaceted approach combining bioinformatics analyses of clinical and experimental datasets, single-cell sequencing, and molecular and pharmacologic manipulation of patient-derived cells identified GSCs expressing immunosuppressive effectors mimicking regulatory T cells (Tregs).
View Article and Find Full Text PDFBMC Cancer
November 2024
Division of Pediatric Neurosurgery, Riley Hospital for Children, Indianapolis, IN, USA.
Cell Mol Life Sci
November 2024
Shilpee Dutt Laboratory, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, 410210, India.
Efficient DNA double strand break (DSB) repair is necessary for genomic stability and determines efficacy of DNA damaging cancer therapeutics. Spatiotemporal dynamics and post-translational modifications of repair proteins at DSBs dictate repair efficacy. Here, we identified a non-canonical function of GCN5 in regulating both HR and NHEJ repair post genotoxic stress.
View Article and Find Full Text PDFJCI Insight
July 2023
Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, USA.
Glioblastomas (GBM) are aggressive tumors that lack effective treatments. Here, we show that the Rho family guanine nucleotide exchange factor Syx promotes GBM cell growth both in vitro and in orthotopic xenografts derived from patients with GBM. Growth defects upon Syx depletion are attributed to prolonged mitosis, increased DNA damage, G2/M cell cycle arrest, and cell apoptosis, mediated by altered mRNA and protein expression of various cell cycle regulators.
View Article and Find Full Text PDFCell Rep
July 2023
Department of Neurosurgery, NYU Grossman School of Medicine, New York, NY 10016, USA; Kimmel Center for Stem Cell Biology, NYU Grossman School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA; Brain and Spine Tumor Center, NYU Grossman School of Medicine, New York, NY 10016, USA; Neuroscience Institute, NYU Grossman School of Medicine, New York, NY 10016, USA. Electronic address:
The adhesion G-protein-coupled receptor GPR133 (ADGRD1) supports growth of the brain malignancy glioblastoma. How the extracellular interactome of GPR133 in glioblastoma modulates signaling remains unknown. Here, we use affinity proteomics to identify the transmembrane protein PTK7 as an extracellular binding partner of GPR133 in glioblastoma.
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